Influence of excipients on thermodynamic phase behavior of pharmaceutical/solvent systems: Molecular thermodynamic model prediction

被引：15

作者：

Chen, Qiao ^{[1
]}

Ji, Yuanhui ^{[1
]}

Ge, Kai ^{[1
]}

机构：

[1] Southeast Univ, Sch Chem & Chem Engn, Jiangsu Prov Hitech Key Lab Biomed Res, Nanjing 211189, Peoples R China

来源：

CHEMICAL ENGINEERING SCIENCE | 2021年 / 244卷

基金：

中国国家自然科学基金;

关键词：

Poorly soluble API; Polymeric excipients; PC-SAFT model; Solubility prediction; Thermodynamic phase behavior; PERTURBED-CHAIN SAFT; SOLID DISPERSIONS; POLYETHYLENE-GLYCOL; CHEMICAL-STABILITY; PHYSICAL STABILITY; BINARY-MIXTURES; IONIC LIQUIDS; SOLUBILITY; ACID; EQUATION;

D O I：

10.1016/j.ces.2021.116798

中图分类号：

TQ [化学工业];

学科分类号：

0817 ;

摘要：

In this work, the influence of polymeric excipients (PEG6000, PEG400, PVPK25, and HPMCE3) on thermodynamic phase behavior of active pharmaceutical ingredients (API) (mesalazine and allopurinol) and its aqueous solution was systematically investigated through experimental measurement and thermodynamic modeling. The API/excipients formulations were prepared by ball milling, and the phase behavior was measured by differential scanning calorimetry (DSC). The results showed that the solubility of API/solvent systems were all increased with higher temperature. Meanwhile, it was found that all four excipients can solubilize mesalazine and allopurinol effectively and the solubilization performance of PVPK25 and HPMCE3 were preferable to PEG. Furthermore, the thermodynamic phase behavior of API in the excipients/water ternary system was predicted by the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), demonstrating good accordance with the experimental results with low average relative deviations (ARDs). This work was expected to provide theoretical guidance for the screening of pharmaceutical formulation excipients. (c) 2021 Elsevier Ltd. All rights reserved.

引用

页数：11

共 59 条

[1] Automation Potential of a New, Rapid, Microscopy-Based Method for Screening Drug-Polymer Solubility [J].

Alhijjaj, Muqdad ;

Belton, Peter ;

Fabian, Laszlo ;

Reading, Mike ;

Qi, Sheng .

ACS OMEGA, 2020, 5 (20) :11402-11410

[2] Evaluation of the bioavailability of hydrocortisone when prepared as solid dispersion [J].

Altamimi, Mohammad A. ;

Elzayat, Ehab M. ;

Qamar, Wajhul ;

Alshehri, Sultan M. ;

Sherif, Abdelrahman Y. ;

Haq, Nazrul ;

Shakeel, Faiyaz .

SAUDI PHARMACEUTICAL JOURNAL, 2019, 27 (05) :629-636

[3] Phase Behavior of Binary Mixtures Containing Succinic Acid or Its Esters [J].

Altuntepe, Emrah ;

Reinhardt, Annika ;

Brinkmann, Joscha ;

Briesemann, Tom ;

Sadowski, Gabriele ;

Held, Christoph .

JOURNAL OF CHEMICAL AND ENGINEERING DATA, 2017, 62 (07) :1983-1993

[4] Predicting Solubility/Miscibility in Amorphous Dispersions: It Is Time to Move Beyond Regular Solution Theories [J].

Anderson, Bradley D. .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2018, 107 (01) :24-33

[5] BDDCS Applied to Over 900 Drugs [J].

Benet, Leslie Z. ;

Broccatelli, Fabio ;

Oprea, Tudor I. .

AAPS JOURNAL, 2011, 13 (04) :519-547

[6] Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances [J].

Bertoni, Serena ;

Albertini, Beatrice ;

Passerini, Nadia .

PHARMACEUTICS, 2020, 12 (06) :1-20

[7] Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study [J].

Brunsteiner, Michael ;

Khinast, Johannes ;

Paudel, Amrit .

PHARMACEUTICS, 2018, 10 (03)

[8] The Role of Polyfunctionality in the Formation of [Ch]Cl-Carboxylic Acid-Based Deep Eutectic Solvents [J].

Crespo, Emanuel A. ;

Silva, Liliana P. ;

Martins, Monia A. R. ;

Buelow, Mark ;

Ferreira, Olga ;

Sadowski, Gabriele ;

Held, Christoph ;

Pinho, Simao P. ;

Coutinho, Joao A. P. .

INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, 2018, 57 (32) :11195-11209

[9] Phase behavior of pharmaceutically relevant polymer/solvent mixtures [J].

Dohrn, Stefanie ;

Luebbert, Christian ;

Lehmkemper, Kristin ;

Kyeremateng, Samuel O. ;

Degenhardt, Matthias ;

Sadowski, Gabriele .

INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2020, 577

[10] Experimental Data of Fluid Phase Equilibria- Correlation and Prediction Models: A Review [J].

Domanska, Urszula .

PROCESSES, 2019, 7 (05)

← 1 2 3 4 5 6 →